<i>Sept7b</i>is essential for pronephric function and development of left-right asymmetry in zebrafish embryogenesis

Dash, S. K.; Lehtonen, Eero; Wasik, Anita A.; Schepis, Antonino; Paavola, Jere; Panula, Pertti; Nelson, W. James

doi:10.1242/jcs.138495

Cited by 27 publications

(34 citation statements)

References 77 publications

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“…Freshly dissected skeletal muscle, kidney, and liver tissues were snap frozen in liquid nitrogen, embedded in Tissue-Tek Optimal Cutting Temperature (OCT) compound (Sakura Finetek, Alphen aan den Rijn, The Netherlands), or fixed in 10% formalin, followed by embedding in paraffin. Quantitative RT-PCR was performed as in Dash et al (23). The primers used to amplify phosphoenolpyruvate carboxykinase 1 ( PCK1 ) were the following: forward 5′-CCAAGAGCAGAGAGACACAG-3′ and reverse 5′-CAATACCAATCTTGGCCAGC-3′ and glucose-6-phosphatase ( G6Pase ) forward 5′-CATCAATCTCCTCTGGGTGG-3′ and reverse 5′-TGCTGTAGTAGTCGGTGTCC-3′.…”

Section: Methodsmentioning

confidence: 99%

Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity

Polianskyte-Prause¹,

Tolvanen²,

Lindfors³

et al. 2018

FASEB j.

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Metformin, the first-line drug to treat type 2 diabetes (T2D), inhibits mitochondrial glycerolphosphate dehydrogenase in the liver to suppress gluconeogenesis. However, the direct target and the underlying mechanisms by which metformin increases glucose uptake in peripheral tissues remain uncharacterized. Lipid phosphatase Src homology 2 domain-containing inositol-5-phosphatase 2 (SHIP2) is upregulated in diabetic rodent models and suppresses insulin signaling by reducing Akt activation, leading to insulin resistance and diminished glucose uptake. Here, we demonstrate that metformin directly binds to and reduces the catalytic activity of the recombinant SHIP2 phosphatase domain in vitro. Metformin inhibits SHIP2 in cultured cells and in skeletal muscle and kidney of db/db mice. In SHIP2-overexpressing myotubes, metformin ameliorates reduced glucose uptake by slowing down glucose transporter 4 endocytosis. SHIP2 overexpression reduces Akt activity and enhances podocyte apoptosis, and both are restored to normal levels by metformin. SHIP2 activity is elevated in glomeruli of patients with T2D receiving nonmetformin medication, but not in patients receiving metformin, compared with people without diabetes. Furthermore, podocyte loss in kidneys of metformin-treated T2D patients is reduced compared with patients receiving nonmetformin medication. Our data unravel a novel molecular mechanism by which metformin enhances glucose uptake and acts renoprotectively by reducing SHIP2 activity.—Polianskyte-Prause, Z., Tolvanen, T. A., Lindfors, S., Dumont, V., Van, M., Wang, H., Dash, S. N., Berg, M., Naams, J.-B., Hautala, L. C., Nisen, H., Mirtti, T., Groop, P.-H., Wähälä, K., Tienari, J., Lehtonen, S. Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity.

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Section: Methodsmentioning

confidence: 99%

Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity

Polianskyte-Prause¹,

Tolvanen²,

Lindfors³

et al. 2018

FASEB j.

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“…Septins play important roles in diverse cellular processes including cytokinesis (Hartwell, 1971; Kinoshita et al, 1997), cell migration (Dolat et al, 2014; Tooley et al, 2009), neuronal morphogenesis (Tada et al, 2007; Xie et al, 2007), and ciliogenesis (Dash et al, 2014; Hu et al, 2010; Kim et al, 2010; Zhai et al, 2014). Dysregulation of such functions has been implicated in cancer, neuropathy, and infertility (Dolat et al, 2014; Hall & Russell, 2004).…”

Section: Introductionmentioning

confidence: 99%

Visualization of in vivo septin ultrastructures by platinum replica electron microscopy

Ong

Svitkina

2016

Methods in Cell Biology

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Septins are cytoskeletal proteins involved in diverse biological processes including cytokinesis, cell morphogenesis, motility, and ciliogenesis. Septins form various filamentous structures in vitro and in vivo, but the higher-order architecture of septin structures in vivo remains poorly defined. The best understood system in this respect is the budding yeast Saccharomyces cerevisiae, where septins form a ring structure that undergoes multiple stages of remodeling during the cell cycle. In this chapter, we describe a method for visualizing supramolecular septin structures in yeast at high spatial resolution using platinum replica electron microscopy. This approach can be applied to further understand the regulation of assembly and remodeling of septin higher-order structures, as well as the relationship between septin architecture and function.

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“…Intriguingly, several zebrafish studies have indicated the importance of septins for the proper formation and function of cilia, where loss-of-function studies have generated several phenotypes that resemble human ciliopathies (Dash et al, 2014). Hence, an understanding of the role of septins in ciliogenesis at a cellular level is critical to our understanding of ciliopathies.…”

Section: Flagella and Ciliamentioning

confidence: 99%

“…However, septins have more consistently been localized along the axoneme of cilia in many cell types and animal models (Ghossoub et al, 2013; Dash et al, 2014; Fliegauf et al, 2014; Zhai et al, 2014). For example, using various human cells lines such as RPE1 (human retinal pigment epithelial cell line) and hFE (human inner foreskin), Benmerah and colleagues found SEPT2, SEPT7 and SEPT9 to be co-localized along the axoneme in primary cilia and to regulate ciliary length, yet no rings were reported.…”

Section: Localization Of Septins In Ciliamentioning

confidence: 99%

“…Septins also interact and regulate the exocyst complex by directing it to the correct location and affect the activity of SNARE proteins important in membrane fusion (Beites et al, 1999, 2005; Amin et al, 2008; Estey et al, 2010), suggesting that changes in membrane traffic caused by septins could also impact cilia growth and function. As well, SEPT7 was shown to interact with Rab8 (Dash et al, 2014), a small GTPase that functions in vesicle trafficking and ciliogenesis (Nachury et al, 2007; Yoshimura et al, 2007). Septins could also affect vesicle traffic via the cytoskeleton since they associate with microtubules and guide the direction of microtubule growth (Bowen et al, 2011; Nölke et al, 2016) and may control vesicular transport along them (Spiliotis et al, 2008).…”

Section: What Could Be the Function Of Septins In Primary Cilia?mentioning

confidence: 99%

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Uncovering the Roles of Septins in Cilia

Palander

El-Zeiry

Trimble

2017

Front. Cell Dev. Biol.

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Septins are a family of GTP-binding proteins that associate with cellular membranes and the cytoskeleton. Their ability to polymerize into filamentous structures permits them to serve as diffusion barriers for membrane proteins and as multi-molecular scaffolds that recruit components of signaling pathways. At the cellular level, septins contribute to the regulation of numerous processes, including cytokinesis, cell polarity, cell migration, and many others. In this review, we discuss emerging evidence for roles of mammalian septins in the biogenesis and function of flagella and cilia, and how this may impact human diseases such as ciliopathies.

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Sept7bis essential for pronephric function and development of left-right asymmetry in zebrafish embryogenesis

Cited by 27 publications

References 77 publications

Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity

Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity

Visualization of in vivo septin ultrastructures by platinum replica electron microscopy

Uncovering the Roles of Septins in Cilia

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